U.S. patent application number 13/953565 was filed with the patent office on 2013-11-28 for urea sorbent.
This patent application is currently assigned to The Technion Research and Development Foundation, LTD.. The applicant listed for this patent is Fresenius Medical Care Holdings, Inc., The Technion Research and Development Foundation, LTD.. Invention is credited to Moris S. Eisen.
Application Number | 20130313188 13/953565 |
Document ID | / |
Family ID | 42729831 |
Filed Date | 2013-11-28 |
United States Patent
Application |
20130313188 |
Kind Code |
A1 |
Eisen; Moris S. |
November 28, 2013 |
Urea Sorbent
Abstract
A sorbent polymer is provided that interacts or reacts with
aqueous urea to aid the regeneration of a dialysate liquid. The
sorbent polymer may include one or more specific functional groups
bonded thereto. Such specific functional groups are selected from
carboxylic acids, carboxylic acid esters, carboxylates, amides,
dicarboxylic acids, dicarboxylic acid esters, and dicer boxylates
to produce the desired urea sorbent.
Inventors: |
Eisen; Moris S.; (Kyrat,
IL) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
The Technion Research and Development Foundation, LTD.
Fresenius Medical Care Holdings, Inc. |
Haifa
Waltham |
MA |
IL
US |
|
|
Assignee: |
The Technion Research and
Development Foundation, LTD.
Haifa
MA
Fresenius Medical Care Holdings, Inc.
Waltham
|
Family ID: |
42729831 |
Appl. No.: |
13/953565 |
Filed: |
July 29, 2013 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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13541107 |
Jul 3, 2012 |
|
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13953565 |
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12479513 |
Jun 5, 2009 |
8220643 |
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13541107 |
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61059610 |
Jun 6, 2008 |
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Current U.S.
Class: |
210/502.1 |
Current CPC
Class: |
C08F 216/06 20130101;
C08F 218/10 20130101; C08F 220/06 20130101; B01J 41/00 20130101;
C08F 218/10 20130101; C08F 8/14 20130101; C08F 8/14 20130101; C08F
216/06 20130101; C08F 218/04 20130101; C08F 218/04 20130101; C08F
216/06 20130101; C08F 2800/10 20130101; B01J 20/28052 20130101;
C08F 8/32 20130101; C08F 8/14 20130101; B01D 15/00 20130101; A61P
7/08 20180101; A61M 1/3679 20130101; B01J 20/261 20130101; C08F
8/14 20130101; A61M 1/1696 20130101; C08F 210/02 20130101; C08F
8/50 20130101; C08F 218/10 20130101; C08F 16/06 20130101; C08F
16/06 20130101; C08F 218/10 20130101; C08F 210/02 20130101; C08F
16/06 20130101; C08F 120/06 20130101; C08F 216/06 20130101; C08F
210/02 20130101; C08F 8/14 20130101; B01J 20/264 20130101; C08F
220/54 20130101; C08F 8/14 20130101; C08F 8/32 20130101; C08F
2810/20 20130101; C08F 218/04 20130101; C08F 220/06 20130101; B01J
20/20 20130101; B01J 20/265 20130101 |
Class at
Publication: |
210/502.1 |
International
Class: |
A61M 1/36 20060101
A61M001/36 |
Claims
1. A filter for regenerating dialysate comprising: a sorbent layer
comprising a polymer having specific functional groups bonded
thereto that interact with urea at a pH of between 5 and 10 to
remove urea from an aqueous solution, wherein the polymer is
substantially insoluble in water and interacts with urea in a
predetermined temperature range and without releasing ammonia and
wherein the reaction product of the polymer and urea is
substantially insoluble in water; and activated carbon for
absorbing organic metabolites from the dialysate.
2. The filter of claim 1, further comprising an anion exchange
layer for removing anions from the dialysate.
3. A dialysate regenerating filter for removing solids or liquids
from dialysate comprising: a sorbent layer comprising a polymer
having functional groups bonded thereto that interact or react with
urea at a pH of between 4 to 12 and bind urea from an aqueous
solution, wherein the polymer is either soluble or substantially
insoluble in water and interacts or reacts with urea without
releasing ammonia and wherein the interaction or reaction product
of the polymer and urea is either soluble or substantially
insoluble in water; and activated carbon for absorbing organic
metabolites from the dialysate.
4. The filter of claim 3, further comprising an anion exchange
layer for removing anions from the dialysate.
5. The filter of claim 3, wherein the functional groups interact or
react with urea at a pH of between 6 and 9.
6. The filter of claim 3, wherein the polymer is insoluble in
water.
7. The filter of claim 3, wherein the interaction or reaction
product of the polymer and urea is insoluble in water.
Description
RELATED APPLICATION(S)
[0001] This application is a divisional of U.S. application Ser.
No. 13/541,107, filed Jul. 3, 2012, which is a divisional of U.S.
application Ser. No. 12/479,513, filed Jun. 5, 2009, now U.S. Pat.
No. 8,220,643, which claims the benefit of U.S. Provisional
Application No. 61/059,610, filed on Jun. 6, 2008. The entire
teachings of the above application(s) are incorporated herein by
reference.
TECHNICAL FIELD
[0002] The following disclosure relates to sorbent materials for
separating and/or removing urea from dialysate solutions in
sorbent-based dialysis treatment or for separating and/or removing
urea from aqueous solutions or liquids in medical related processes
or circumstances.
BACKGROUND
[0003] Hemodialysis is a process by which toxins and other
molecules, such as urea, are removed from the blood using a
semi-permeable filtering membrane. Typically, the patient's blood
and an aqueous solution (i.e., dialysate) are pumped in
counter-direction flows in and about hollow, semi-permeable fibers.
In FIG. 1 a known configuration of a dialyzer is shown. Generally,
blood flows in one end of the dialyzer and through hollow
semi-porous or semipermeable fibers toward the blood output side of
the dialyzer. Meanwhile, dialysate flows in an opposite direction,
with respect to the blood flow, by entering a dialysate inlet and
flowing around or about the semi-porous hollow fibers in which the
blood is flowing. The dialysate then exits the dialysate outlet.
The toxins within the blood are removed from the blood via a
combination of diffusion, convection, and osmosis processes while
the blood is flowing within the fibers and the dialysate is flowing
outside the fibers. Generally, the dialyzer is comprised of a large
number of semi-permeable hollow fibers bundled together and placed
in a cylindrical jacket as shown. Present day dialysis processes
may be classified as: 1) single pass; and 2) sorbent-based. Single
pass processes require a continuous supply of gallons of fresh and
treated water. The treated water may be purified by for example,
reverse osmosis or distillation. The gallons of fresh and treated
water are used to create the dialysis fluid, which is discarded
after flowing through the dialyzer and collecting the toxins in a
single pass through of the dialyzer.
[0004] FIG. 2 shows a schematic/diagram of a cross section of a
single semi-permeable fiber that may be used in a dialyzer. The
blood flows through the hollow lumen within the semi-permeable
walls of the fiber. The membrane walls have a thickness, which is
the difference of the radius R2 minus the radius R1. The membrane
is semi-permeable and the dialysate, as shown, flows in the
opposite direction outside of the semi-permeable fiber.
[0005] Sorbent dialysis differs from single pass dialysis in that
the dialysate is regenerated using a series of chemical powders to
remove toxins from the dialysate solution. Typically, spent
dialysate from the dialyzer is pumped through the first chemical
layer of an enzyme called "urease". The urease catalyzes the
breakdown of urea into ammonia and carbon dioxide. The dialysate
will then pass through a second chemical layer, a cation exchange
layer (zirconium phosphate) which absorbs ammonia and other
positively charged ions and then through a third, chemical layer,
an anion exchange layer (hydrous zirconium oxide) where anions such
as phosphate and fluoride are absorbed. Finally, the dialysate is
pumped through a fourth layer of activated carbon where organic
metabolites such as creatinine are absorbed. At some point, the
filtered dialysate may be passed through a degasser to remove air,
carbon dioxide and other gas bubbles that may form or be found in
the dialysate.
[0006] The capacity of the zirconium phosphate cation exchange
layer to absorb ammonia is limited by the number of sites available
to bind ammonia. If the zirconium phosphate layer is depleted,
ammonia will remain in the dialysate as it is recycled to the
dialyzer. In this case the patient may be at risk of ammonia
toxicity. Consequently, the filtered dialysate must be periodically
tested or monitored for ammonia concentration.
[0007] A typical dialysis patient generates an excess of about 24
to about 60 grams of urea per day that must be removed from the
blood to avoid uremia. Therefore, what is needed is a sorbent for
use in dialysis that has the capacity to remove this quantity of
urea in a reasonable time frame. Thus, suitable sorbents should
have the capacity to remove approximately 2.5 grams per deciliter
of dialysate per hour (gm/dl/hr) from the dialysate.
SUMMARY
[0008] In one embodiment, a urea sorbent is provided that is
suitable for use in a sorbent-based dialysis process. The sorbent
absorbs urea from the dialysate without generating ammonia or
carbon dioxide, thereby eliminating the need for monitoring the
concentration of ammonia in the dialysate as well as reducing or
eliminating the need for de-gassing the dialysate. In one
variation, the sorbent is insoluble or substantially insoluble in
water and effective to remove urea from dialysate in a pH range of
between 4 and 12 and more particularly in a pH range of between
about 6 and 8. In another embodiment the sorbent is soluble or
substantially soluble and effective to bond with urea to remove, or
bind urea from a dialysate solution or other aqueous solution.
[0009] In another aspect, a filter for regenerating dialysate
includes a sorbent layer comprising a polymer having specific
functional groups bonded thereto that interact or react with urea
at a pH of between 4 and 12, and more particularly at a pH of
between 6 and 8, to remove urea from an aqueous solution. The
exemplary polymer may be any one of soluble, substantially soluble,
insoluble and substantially insoluble in water. The exemplary
polymer further reacts or interacts with urea while near room
temperature or while in a defined temperature range between about
50.degree. F. and 110.degree. F. without releasing ammonia or
generating carbon dioxide. The reaction product of the polymer and
urea may also be any one of soluble, substantially soluble,
insoluble and substantially insoluble in water. A second filter
layer may be used with the exemplary polymer sorbent. The second
filter layer comprises activated carbon for absorbing organic
metabolites from the dialysate or other aqueous solution. In one
variation, the filter further includes an anion exchange layer for
removing anions from the dialysate.
[0010] In another aspect, a filter for removing urea from an
aqueous solution or liquid is provided. The filter comprises a
sorbent layer or coating. The sorbent layer or coating comprises a
polymer having specific functional groups bonded thereto. The
exemplary polymer having specific functional groups bonded thereto
interacts or reacts with urea at a pH of between 4 and 12 or a
predetermined bounded pH range therebetween (i.e., 3 to 7, 5-9,
6-8, etc.) Upon interaction or perhaps a reaction with urea, urea
is bonded to the exemplary sorbent polymer and removed from an
aqueous solution. An exemplary polymer may be soluble,
substantially soluble, insoluble, or substantially insoluble in
water. Furthermore, an exemplary polymer reacts with urea at near
room temperature or other predetermined temperature range without
releasing ammonia or generating carbon dioxide. In various aspects,
an exemplary polymer reacts or interacts with urea to produce a
single reaction product. The filter may also include activated
carbon for adsorbing and removing other molecules from the aqueous
solution. The reaction product produced by the reaction or
interaction of an exemplary polymer and urea may be soluble,
substantially soluble, insoluble, or substantially insoluble in
water.
BRIEF DESCRIPTION OF THE DRAWINGS
[0011] For a more complete understanding, reference is now made to
the following description taken in conjunction with the
accompanying Drawings in which:
[0012] FIG. 1 illustrates a diagram of a dialyzer; and
[0013] FIG. 2 illustrates a cross-sectional diagram of a fiber
lumen in a dialyzer.
DETAILED DESCRIPTION
[0014] Referring now to the drawings, the various views and
embodiments of exemplary urea sorbents are illustrated and
described, and other possible embodiments are described. The
figures are not necessarily drawn to scale, and in some instances
the drawings have been exaggerated and/or simplified in places for
illustrative purposes only. One of ordinary skill in the art will
appreciate the many possible applications and variations based on
the following examples of possible embodiments.
[0015] Sorbent Preparation:
1. Preparation of MPS-IV-048 (Polyvinylglyoxalate)
##STR00001##
[0017] 1.1 Reagents
TABLE-US-00001 Entry Reagent/solvent Amount mmol Equivalent 1
Polyvinyl alcohol 1.000 g 5.0 .times. 10.sup.-3 1 (M. wt. = 205000)
(23.3 mmol of alcohol units) 2 Glyoxylic acid 2.144 g 23.30 1
monohydrate (M. wt. = 92) 3 EDC.cndot.HC1 (M. wt. = 3.973 g 20.72
0.88 191.71) 4 Distilled water 15 ml
[0018] 1.2 Procedure.
[0019] To a stirred solution of glyoxylic acid monohydrate and
EDC.HCl in distilled water, polyvinyl alcohol was added stirred the
solution for 24 h. Water was evaporated under reduced pressure to
obtain a gum, which was used for urea trapping experiments from the
dialysis solutions.
2. Preparation of MPS-IV-054 (Polyvinylglyoxalate)
##STR00002##
[0021] 2.1 Reagents
TABLE-US-00002 Entry Reagent/solvent Amount mmol Equivalent 1
Polyvinyl alcohol (M. 1.000 g 5.0 .times. 10.sup.-3 1 wt. = 205000)
(23.3 mmol of alcohol units) 2 Glyoxylic acid 2.144 g 23.30 1
monohydrate (M. wt. = 92) 3 NaH (M. wt. = 1.538 g 0.846 1.51 24
55-60% in suspension) 4 Dry-N,N- 10 ml Dimethylformamide (DMF)
[0022] 2.2 Procedure
[0023] Sodium hydride was added to a cooled (0.degree. C., ice
bath) stirred suspension of polyvinyl alcohol in dry DMF and
stirring continued for 2-3 min. Glyoxylic acid monohydrate was
added to this mixture and the mixture was brought to room
temperature after 2 h stirring at 0.degree. C. Stirring continued
for overnight. The solid obtained was washed with DCM and used for
urea trapping experiments from the dialysis solutions.
[0024] 2.3 Properties [0025] Weight of MPS-IV-054=3.691 g [0026]
Melting Point of MPS-IV-054=doesn't melt up to 290 0.degree. C.
[0027] Mn=75540; Mw=79736; .rho.=1.055 g/cm3
3. Preparation of MPS-V-003 (Bis(Polyvinyloxalate))
##STR00003##
[0029] 3.1 Reagents
TABLE-US-00003 Entry Reagent/solvent Amount mmol Equivalent 1
Polyvinyl alcohol 1.000 g 5.0 .times. 10.sup.-3 1 (M. wt. = 205000)
(23.3 mmol of alcohol units) 2 Oxalic acid (M. wt. = 2.000 g 25.64
1.1 78) 3 EDC.cndot.HC1 (M. wt. = 3.973 g 20.72 0.88 191.71) 4
Distilled water 20 ml
[0030] 3.2 Procedure
[0031] To a stirred solution of oxalic acid and EDC.HCl in
distilled water, polyvinyl alcohol was added stirred the solution
for 24 h. Water was evaporated under reduced pressure to obtain a
gum, which was used for urea trapping experiments from the dialysis
solutions.
[0032] 3.3 Properties [0033] Weight of MPS-V-003=6.20 g
4. Preparation of MPS-V-004 (Polyvinylpyruvate)
##STR00004##
[0035] 4.1 Reagents
TABLE-US-00004 Entry Reagent/solvent Amount mmol Equivalent 1
Polyvinyl alcohol 1.000 g 5.0 .times. 10.sup.-3 1 (M. wt. = 205000)
(23.3 mmol of alcohol units) 2 Pyruvic acid 2.10 ml 25.28 1.1 (M.
wt. = 88.06; d = (.ident.2.226 g) 1.06) 3 EDC.cndot.HC1 (M. wt. =
3.92 g 20.44 0.88 191.71) 4 Distilled water 15 ml
[0036] 4.2 Procedure
[0037] To a stirred solution of pyruvic acid and EDC.HCl in
distilled water, polyvinyl alcohol was added stirred the solution
for 24 h. Water was evaporated under reduced pressure to obtain a
gum, which was used for urea trapping experiments from the dialysis
solutions.
[0038] 4.3 Properties [0039] Weight of MPS-V-004=6.42 g
5. Preparation of MPS-V-005 (Polyvinylbezoate 0.33 Polyvinylalcohol
0.66)
##STR00005##
[0041] 5.1 Reagents
TABLE-US-00005 Entry Reagent/solvent Amount mmol Equivalent 1 2.000
g 1.0 .times. 10.sup.-2 1 .times. 10.sup.-2 1 Polyvinyl (46.6 mmol
(46.6 mmole alcohol of alcohol of alcohol (M. wt. = units) units)
205000) 2 Benzoyl chloride 2.00 ml 17.23 0.37 (M. wt. =
(.ident.2.422 g) 130.57; d = 1.211) 3 Dry pyridine 25 ml
[0042] 5.2 Procedure
[0043] To a stirred, cooled (0.degree. C., ice bath) solution of
polyvinyl alcohol in dry pyridine (17 ml), a solution of benzoyl
chloride in dry pyridine (8 ml) was added dropwise over a period of
10 min and stirring continued for 24 h with gradual increase in
reaction temperature to rt. After 24 h, the pyridine was removed
under reduced pressure and by co-evaporation with toluene to obtain
a gum which was used for next step. The gum (MPS-V-005) swelled
when brought in contact with solvents like ethyl acetate,
dichloromethane (DCM), chloroform and methanol.
6. Preparation of MPS-IV-009 (Polyvinylbezoate 0.33
Polyvinylglyoxalate 0.66)
##STR00006##
[0045] 6.1 Reagents
TABLE-US-00006 Entry Reagent/solvent Amount mmol Equivalent 1
MPS-V-005 2.000 g (29.3 mmol of 1 alcohol units) 2 Glyoxylic acid
0.920 g 10.00 0.34 monohydrate (M. wt. = 92) 3 EDC.cndot.HC1 (M.
1.55 g 10.00 0.34 wt. = 191.71) 4 Distilled water 20 ml
[0046] 6.2 Procedure
[0047] A solution of glyoxylic acid monohydrate and EDC.HCl in
distilled water was added to MPS-V-005 and the suspension was
stirred at room temperature for 48 h. The white ppt obtained was
filtered off, dried and used for urea trapping experiments from the
dialysis solutions.
[0048] 6.3 Properties [0049] Weight of MPS-V-009=1.543 g
7. Preparation of MPS-V-027 (Polyvinylglyoxalate-Ethylene
Copolymer)
##STR00007##
[0051] 7.1 Reagents
TABLE-US-00007 Entry Reagent/solvent Amount mmol Equivalent 1
Polyvinyl alcohol- 2.28 g 41.67 mmol 1 coethylene (27%
(.ident.1.838 g of of ethylene) polyvinyl alcohol) OH group 2
Glyoxalic acid 4.00 g 43.48 1.04 monohydrate (M. wt. = 92) 3 NaH
(M. wt. = 1.200 g 50.00 1.2 24 55-60% in suspension) 4 Thionyl
chloride 12 (.ident.19.572 g) 164.51 3.78 (M. wt. = 118.97, d =
1.613) 5 Dry-N,N- 30 ml Dimethylformamide (DMF)
[0052] 7.2 Procedure
[0053] Glyoxylic acid monohydrate was dissolved in thionyl chloride
and the mixture was refluxed for 48 h. Removal of excess thionyl
chloride under vacuum gave a gum (glyoxaloyl chloride). Polyvinyl
alcohol co-ethylene was dissolved in dry DMF (by warming up to
100.degree. C.) and this solution was added (after cooling to about
40.degree. C.) to the previously obtained gum. The mixture was
stirred for about 30 min in ice bath and NaH was added. Stirring
continued for overnight after removal of the ice bath to obtain a
sticky solid which was used for the urea trapping experiments from
the dialysis solutions.
[0054] 7.3 Properties [0055] Weight of MPS-V-027=4.763 g
8. Preparation of MPS-V-036
[0056]
(polyacrylicacid.sub.0.9polyvinylpolyacrylicacid.sub.0.1)
##STR00008##
[0057] 8.1 Reagents
TABLE-US-00008 Entry Reagent/solvent Amount mmol Equivalent 1
Poly(acrylic acid) 1.500 g 3.75 .times. 10.sup.-4 1 (M. wt. =
4000000) (20.83 mmol of --COOH units) 2 Polyvinyl alcohol 1.000 g
4.88 .times. 10.sup.-4 0.1 (M. wt. = 205000) (2.27 mmol of --OH
units) 3 EDC.cndot.HC1 0.479 g 2.49 1.1 eq of --OH (M. wt. =
191.71) groups 4 Distilled water 50 ml
[0058] 8.2 Procedure
[0059] Poly (acrylic acid) was added to a stirred solution of
EDC.HCl in distilled water. To this stirred suspension, polyvinyl
alcohol was added and the solution was stirred for overnight. The
gel obtained was filtered under suction (vacuum pump), washed with
water, methanol, dichloromethane (DCM), acetone and ether
respectively and dried for one week at room temperature to obtain a
glassy solid, which was used for urea trapping experiments from the
dialysis solutions.
[0060] 8.3 Properties [0061] Weight of MPS-V-036=3.361 g
9. Preparation of MPS-V-037 (Polyvinylpyrurate-Ethylene
Copolymer)
##STR00009##
[0063] 9.1 Reagents
TABLE-US-00009 Entry Reagent/solvent Amount mmol Equivalent 1
Polyvinyl alcohol- 1.14 g 20.84 mmol 1 coethylene (27%
(.ident.0.909 g of of OH group ethylene) polyvinyl alcohol) 2
Pyruvic acid 1.90 ml 27.19 1.3 (M. wt. = (.ident.2.394 g) 88.06, d
= 1.26) 3 DCC 6.450 g 31.26 1.5 (M. wt. 206.33) 4 DMAP (M. wt. =
0.382 g 3.13 0.15 122.17) 5 Dry-N,N- 30 ml Dimethylformamide
(DMF)
[0064] 9.2 Procedure
[0065] Polyvinyl alcohol co-ethylene was dissolved in DMF (15 ml)
by heating the mixture to 100.degree. C. This solution (after
cooling to 40.degree. C.) was added to a mixture of pyruvic acid,
dicyclohexyl carbodiimide (DCC) and 4-dimethylaminopyridine (DMAP)
in dry DMF (15 ml) and the reaction mixture was stirred at room
temperature for overnight. The solid obtained was filtered off,
washed with water, methanol, dichloromethane (DCM), acetone and
ether respectively, dried and used for the urea trapping
experiments from the dialysis solutions.
[0066] 9.3 Properties [0067] Weight of MPS-V-037=6.305 g
10. Preparation of MPS-V-038 (Polyvinylglyoxalate-Ethylene
Copolymer)
##STR00010##
[0069] 10.1 Reagents
TABLE-US-00010 Entry Reagent/solvent Amount mmol Equivalent 1
Polyvinyl alcohol- 1.14 g 20.84 mmol 1 coethylene (27%
(.ident.0.909 g of of OH group ethylene) polyvinyl alcohol) 2
Glyoxylic acid 2.400 g 26.09 1.25 monohydrate (M. wt. = 92) 3 DCC
(M. wt. = 6.450 g 31.26 1.5 206.33) 4 DMAP (M. wt. = 0.382 g 3.13
0.15 122.17) 5 Dry-N,N- 30 ml Dimethylformamide (DMF)
[0070] 10.2 Procedure
[0071] Polyvinyl alcohol co-ethylene was dissolved in DMF (15 ml)
by heating the mixture to 100.degree. C. This solution (after
cooling to 40.degree. C.) was added to a mixture of glyoxylic acid
monohydrate, dicyclohexyl carbodiimide (DCC) and
4-dimethylaminopyridine (DMAP) in dry DMF (15 ml) and the reaction
mixture was stirred at room temperature for overnight. The solid
obtained was filtered off, washed with water, methanol,
dichloromethane (DCM), acetone and ether respectively, dried and
used for the urea trapping experiments from the dialysis
solutions.
[0072] 10.3 Properties [0073] Weight of MPS-V-038=6.025 g
11. Preparation of MPS-V-047 (Isopropylaminepolyacrylicamide)
##STR00011##
[0075] 11.1 Reagents
TABLE-US-00011 Entry Reagent/solvent Amount mmol Equivalent 1
Poly(acrylic acid) 1.500 g 3.75 .times. 10.sup.-4 1 (M. wt. =
4000000) (20.83 mmol of --COOH units) 2 iso-Propylamine (M. 0.20 ml
2.33 0.11 wt. = 59.11, d = (.ident.0.138 g) 0.688) 3 EDC.cndot.HC1
(M. wt. = 0.479 g 2.49 1.1 eq of 191.71) --OH groups 4 Distilled
water 50 ml
[0076] 11.2 Procedure
[0077] Poly(acrylic acid) was added to a stirred solution of
EDC.HCl in distilled water. To this stirred suspension,
iso-propylamine was added and the solution was stirred for
overnight. The gel obtained was filtered under suction (vacuum
pump), washed with water, methanol, dichloromethane (DCM), acetone
and ether respectively and dried for one week at room temperature
to obtain a thick gel (like a glassy solid), which was used for
urea trapping experiments from the dialysis solutions.
[0078] 11.3 Properties [0079] Weight of MPS-V-047=2.46 g
[0080] Dialysate solutions were analyzed for nitrogen content and
the amount of urea in the dialysate was calculated. In some cases,
additional urea was added to the solution as indicated in column 2
of each Table (1-5). The polymer reagent was added to the solution
in the amount indicated in column 3. The mixture was stirred at
room temperature for one hour and filtered. The filtrate was
analyzed and the amount of urea removed from the dialysate solution
was determined. A minus sign (-) indicates that the results were
inconclusive.
[0081] In the following tables, the title identifies the particular
polymer reagent tested. The first column of each table represents
the experiment or run number. The second column identifies the
particular dialysate solution used for the experiment and whether
additional urea was added to the solution. The third column
indicates the amount of polymer reagent used in the experiment. The
fourth column gives the reaction conditions e.g. time and
temperature. (Note: rt=room temperature). It is further understood
that room temperature is between about 60 and 78.degree. F. (about
15.56.degree. C. to about 25.56.degree. C.) and that reactions will
also occur in a temperature range of between about 50.degree. F. to
about 110.degree. F. (about 10.degree. C. to about 43.3.degree.
C.). It is believed that reactions will also occur at colder or
warmer temperatures, but such reactions have not been specifically
tested. The fifth column identifies the analyzed portion of the
reaction mixture (e.g. filtrate). In some cases, a neutralizing
agent was added to the filtrate. The sixth column (BUN or Blood
Urea Nitrogen) provides the concentration of nitrogen in the
particular dialysate solution used for the experiment. The seventh
column gives the amount of urea in the solution. The eighth column
contains the maximum amount of urea in the solution. In the cases
where additional urea was added as indicated in column 2, this
number will be higher than the corresponding entry in the sixth
column. The ninth column is the amount of urea removed from the
dialysate solution. The first row of each table provides the
nitrogen, urea and maximum or total amount of urea present in the
dialysate solution used in the experiments.
TABLE-US-00012 TABLE 1 MPS-IV-048 Results (in mg/dL) Amount of
Analyzed Blood Blood Maximum Amount Reagent portion of Urea Urea
amount of of urea Soln Used Reaction reaction Nitrogen (BUN .times.
urea taken out Entry compn (g) condn. mixture (BUN) 2.14) present
(mg/dL/h) 1 Soln-3 -- -- -- 7.8 16.692 16.692 -- Blank (10 ml) 2
Soln-3 2 rt, 1 h Filtrate 14.6 31.244 16.692 (-) 14.552 (10 ml) (8
mL) 3 Soln-3 13 rt, 1 h Filtrate 797.2 1706.0 2516.7 810.7 (20 ml)
+ (0.50 g) (10 mL) Urea (0.50 g)
TABLE-US-00013 TABLE 2 MPS-IV-OS4 and MPS-V-009 Results (in mg/dL)
Analyzed Amount Amount of portion Blood Blood Maximum of urea
Reagent of Urea Urea amount of taken Soln Used Reaction reaction
Nitrogen (BUN .times. urea out Entry compn (g) condn. mixture (BUN)
2.14) present (mg/dL/h) 1 Soln-3 -- -- -- 4 8.56 8.56 -- Blank (10
ml) MPS-IV-054 2 Soln-3 2.5 rt, 1 h Filtrate 2227 4765.78 5008.56
242.78 (20 ml) + (5 ml; Urea pH = 10) (0.50 g) 3 Soln-3 2.50 rt, 1
h Filtrate 2523 5399.22 5008.56 (-) (10 ml) + (3 ml; 390.66 Urea pH
= 10) + (1.00 g) 2% HCI- (0.4 ml) to neutralize to pH = 7 MPS-V-009
4 Soln-3 1.26 rt, 1 h Filtrate 2563 5484.82 2508.56 (-) (10 ml) +
(3 ml; 2976.26 Urea pH = 7) (0.50 g)
TABLE-US-00014 TABLE 3 MPS-V-003 Results (in mg/dL) Amount of
Analyzed Blood Blood Maximum Amount Reagent portion of Urea Urea
amount of of urea Soln Used Reaction reaction Nitrogen (BUN .times.
urea taken out Entry compn (g) condn. mixture (BUN) 2.14) present
(mg/dL/h) 1 Soln-3 -- -- -- 4 8.56 8.56 -- (10 ml) Blank 2 Soln-3
rt, 1 h Filtrate 2257 4740 5008 268.3 (20 ml) + (5 mL; Urea pH = 1)
(1.00 g) 3 Soln-3 rt, 1 h Filtrate 1527 3267.78 5008 1740.22 (20
ml) + (3 m; Urea pH = 1) + (1.00 g) saturated HCO3 (1 ml) to
neutralize to pH = 7
TABLE-US-00015 TABLE 4 MPS-V-027 and MPS-V-036 Results (in mg/dL)
Amount Amount Analyzed Blood Blood Maximum of urea of portion of
Urea Urea amount of taken Soln Reagent Reaction reaction Nitrogen
(BUN .times. urea out Entry compn Used (g) condn. mixture (BUN)
2.14) present (mg/dL/h) 1 Soln-4 -- -- -- 88 188.32 188.32 -- Blank
(9 ml) 2 Soln-4 MPS-V rt, 1 h Filtrate 0 0 2688.32 2688.32 (10 ml)
+ 036 (2 ml) Urea (residue (pH = 6~7) (0.50 g) after filtration)
(2.28 g) 3 Soln-4 MPS-V rt, 1 h Filtrate 1114 2339.4 2688.32 349.3
(10 ml) + 027 (4 ml) Urea (residue (pH = 7~8) (0.50 g) after
filtration and washing with MeOH) (4.40 g)
TABLE-US-00016 TABLE 5 MPS-V-037, MPS-V-038 and MPS-V-047 Data for
Solution-4 Results (in mg/dL) Amount Amount Analyzed Blood Blood
Maximum of urea of portion of Urea Urea amount of taken Soln
Reagent Reaction reaction Nitrogen (BUN .times. urea out Entry
compn Used (g) condn. mixture (BUN) 2.14) present (mg/dL/h) 1
Soln-4 -- -- -- 25 53..5 53..5 -- Blank (9 ml) 2 Soln-4 2 rt, 1 h
Filtrate 0 0 5053.5 5053.5 (20 ml) + (10 ml) Urea (pH-7) (1.00 g) 3
Soln-4 13 rt, 1 h Filtrate 0 0 2553.5 2553.5 (10 ml) + (0.50 g) (10
ml) Urea (pH-7) (0.50 g) 4 Soln-4 MPS-V rt, 1 h Filtrate 479
1025.06 2553.5 1528.44 (10 ml) + 047 (5 ml) Urea (2.46 g) (pH = 5)
(0.50 g)
[0082] As will be appreciated from the foregoing, vinyl polymers
having specific functional groups selected from carboxylic acids,
esters and salts, amides, dicarboxylic acids, and esters and salts
may be formulated to provide sorbents suitable for use in removing
urea from an aqueous solution having a pH from about 6 to 8. Other
sorbents suitable for removing urea from an aqueous solution having
a pH range from 4 to 12 are realizable with various ones of the
aforementioned specific functional groups by one of ordinary skill
in the art having the information contained herein. Such exemplary
polymers are substantially insoluble in water and can remove urea
from dialysate at a rate of at least 2.5 mg/dl/hr. Additionally,
such polymers may be soluble, substantially soluble or insoluble in
water depending on variations in their manufacture.
[0083] In some variations of the invention, vinyl polymers such as
polyvinyl alcohol, polyvinyl alcohol-ethylene co-polymers and
polyacrylic acid are reacted with specific functional groups
selected from carboxylic acids, carboxylic acid esters,
carboxylates, amides, dicarboxylic acids, dicarboxylic acid esters,
and dicarboxylates to produce the desired exemplary sorbents.
Exemplary polymers may be applied to various substrates for use as
dialysis sorbents. Such substrates may be organic or inorganic and
may include filter paper, plastic or glass beads and other
particulate materials that are insoluble in water. The polymers may
also be applied to various screens and mesh-type filter materials
formed from wire or plastic strands or cloth.
[0084] Another advantage of an exemplary urea sorbent is the use of
selective functional groups that can be utilized to make a variety
of resultant exemplary sorbents ranging from being soluble,
insoluble, a liquid, a gum, an adhesive, a flexible material, a
coating as well as a solid or powder.
[0085] It will be appreciated by those skilled in the art having
the benefit of this disclosure that this urea sorbent provides a
viable replacement for prior known dialysis sorbent materials. It
should be understood that the drawings and detailed description
herein are to be regarded in an illustrative rather than a
restrictive manner, and are not intended to be limiting to the
particular forms and examples disclosed. On the contrary, included
are any further modifications, changes, rearrangements,
substitutions, alternatives, design choices, and embodiments
apparent to those of ordinary skill in the art, without departing
from the spirit and scope hereof, as defined by the following
claims. Thus, it is intended that the following claims be
interpreted to embrace all such further modifications, changes,
rearrangements, substitutions, alternatives, design choices, and
embodiments.
[0086] While this invention has been particularly shown and
described with references to example embodiments thereof, it will
be understood by those skilled in the art that various changes in
form and details may be made therein without departing from the
scope of the invention encompassed by the appended claims.
* * * * *